Regulating transient and sustained changes of cytosolic Ca2+ in rat pancreatic acini.
The regulation of changes in cytosolic Ca2+ concentration (Cai2+) during exposure to carbachol was studied in rat pancreatic acini loaded with fura-2. With an extracellular Ca2+ concentration (Cao2+) of 2.5 mM, resting Cai2+ is 185 +/- 48 (SD) nM (n = 23), which rises to 696 +/- 222 nM, then falls over 2 min to a stable plateau of 401 +/- 106 nM. With Cao2+ less than 10 nM, carbachol produces an immediate threefold increase in Cai2+ that dissipates over 2-3 min, and Cai2+ steadily falls below prestimulation levels. Atropine prevents all responses to carbachol, and when it is added during a response to carbachol, Cai2+ drops to resting values within seconds. Ca2+ influx is required for the prolonged elevation of Cai2+ during carbachol exposure, but Ca2+ entry is not regulated by an increase in Cai2+ itself nor does Ca2+ enter via voltage-gated L-type channels. The muscarinic receptor-operated Ca2+ entry mechanism is sensitive to Cao2+, since sustained elevations in Cai2+ are maximal at 2.5 mM Cao2+ but are much less pronounced at lower external Ca2+ concentrations.
Hurley
T W
TW
Department of Child Health, University of Missouri School of Medicine, Columbia 65212.
Brinck
R W
RW
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001572:Benzofurans; D002118:Calcium / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D002478:Cells, Cultured; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D005456:Fluorescent Dyes; D016257:Fura-2; D015759:Ionomycin / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D010179:Pancreas / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D001572:Benzofurans; D005456:Fluorescent Dyes; D015759:Ionomycin; D001285:Atropine; D002217:Carbachol; D002118:Calcium; D016257:Fura-2